Perindopril Erbumine

5 WARNINGS AND PRECAUTIONS Watch for anaphylactoid reactions, including angioedema. (5.1) Monitor renal function during therapy. (5.5) Assess for hypotension and hyperkalemia. (5.2 , 5.6) 5.1 Anaphylactoid and Possibly Related Reactions Presumably because angiotensin-converting enzyme inhibitors affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving ACE inhibitors (including perindopril erbumine) may be subject to a variety of adverse events, some of them serious. Black patients receiving ACE inhibitors have a higher incidence of angioedema compared to nonblacks. Head and Neck Angioedema: Angioedema of the face, extremities, lips, tongue, glottis, or larynx has been reported in patients treated with ACE inhibitors, including perindopril erbumine (0.1% of patients treated with perindopril erbumine in U.S. clinical trials). Angioedema associated with involvement of the tongue, glottis or larynx may be fatal. In such cases, discontinue perindopril erbumine treatment immediately and observe until the swelling disappears. When involvement of the tongue, glottis, or larynx appears likely to cause airway obstruction, administer appropriate therapy, such as subcutaneous epinephrine solution 1:1000 (0.3 to 0.5 mL), promptly. Patients taking concomitant mTOR inhibitor (e.g., temsirolimus) therapy or a neprilysin inhibitor may be at increased risk for angioedema [see Drug Interactions (7.9 ; 7.10) ]. Intestinal Angioedema: Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain. 5.2 Hypotension Perindopril erbumine can cause symptomatic hypotension. Perindopril erbumine has been associated with hypotension in 0.3% of uncomplicated hypertensive patients in U.S. placebo-controlled trials. Symptoms related to orthostatic hypotension were reported in another 0.8% of patients. Symptomatic hypotension is most likely to occur in patients who have been volume or salt-depleted as a result of prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea or vomiting [see Dosage and Administration (2.1) ] . ACE inhibitors may cause excessive hypotension, and may be associated with oliguria or azotemia, and rarely with acute renal failure and death. In patients with ischemic heart disease or cerebrovascular disease, an excessive fall in blood pressure could result in a myocardial infarction or a cerebrovascular accident. In patients at risk of excessive hypotension, perindopril erbumine therapy should be started under very close medical supervision. Patients should be followed closely for the first two weeks of treatment and whenever the dose of perindopril erbumine and/or diuretic is increased. If excessive hypotension occurs, the patient should be placed immediately in a supine position and, if necessary, treated with an intravenous infusion of physiological saline. Perindopril erbumine treatment can usually be continued following restoration of volume and blood pressure. 5.3 Neutropenia/Agranulocytosis ACE inhibitors have been associated with agranulocytosis and bone marrow depression, most frequently in patients with renal impairment, especially patients with a collagen vascular disease such as systemic lupus erythematosus or scleroderma. 5.4 Fetal Toxicity Pregnancy Category D Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected discontinue perindopril erbumine as soon as possible [see Use in Specific Populations (8.1) ]. 5.5 Impaired Renal Function As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. Renal function should be monitored periodically in patients receiving perindopril erbumine [see Dosage and Administration (2.3) ], [see Drug Interactions (7)]. In patients with severe congestive heart failure, where renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with ACE inhibitors, including perindopril erbumine, may be associated with oliguria, progressive azotemia, and, rarely, acute renal failure and death. In hypertensive patients with unilateral or bilateral renal artery stenosis, increases in blood urea nitrogen and serum creatinine may occur; usually reversible upon discontinuation of the ACE inhibitor. In such patients, renal function should be monitored during the first few weeks of therapy. Some perindopril erbumine-treated patients have developed minor and transient increases in blood urea nitrogen and serum creatinine especially in those concomitantly treated with a diuretic. 5.6 Hyperkalemia Elevations of serum potassium have been observed in some patients treated with ACE inhibitors, including perindopril erbumine. Most cases were isolated single values that did not appear clinically relevant and were rarely a cause for withdrawal. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus and the concomitant use of agents such as potassium-sparing diuretics, potassium supplements and/or potassium-containing salt substitutes [see Drug Interactions (7.2) ] . Serum potassium should be monitored periodically in patients receiving perindopril erbumine. 5.7 Cough Presumably because of the inhibition of the degradation of endogenous bradykinin, persistent nonproductive cough has been reported with all ACE inhibitors, generally resolving after discontinuation of therapy. Consider ACE inhibitor-induced cough in the differential diagnosis of cough. 5.8 Hepatic Failure Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and sometimes death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up. 5.9 Surgery/Anesthesia In patients undergoing surgery or during anesthesia with agents that produce hypotension, perindopril erbumine may block angiotensin II formation that would otherwise occur secondary to compensatory renin release. Hypotension attributable to this mechanism can be corrected by volume expansion.